PROJECT SUMMARY The Proteomics & Biophysics Core (Core B) will provide high-quality reagents and services to support all projects in the program. The reagents include recombinant tau and TREM2 proteins as well as synthetic A? peptides. The Core will also perform comprehensive biophysical measurements on proteins to provide structural information. Additionally, mass spectrometry-based methods, such as quantitative proteomics, hydroxyl radical protein footprinting and mass spectrometry imaging, will be utilized to analyze the chemical composition and spatial distribution of A? and tau aggregates in brain sections, as well as conformational ?footprints? of both A? and tau prions. In addition to using standard ?best-practice? technologies, we will develop and implement several emerging techniques that have recently shown great promise by us and others in the field. For example, hydroxyl radical protein footprinting has been used to study soluble proteins and, more recently, applied to amyloids. This method will be used to obtain conformational differences among prion strains. Moreover, mass spec imaging and traditional immunohistochemistry complement each other. When combined, these two methods will provide more detailed information about the chemical composition and much higher spatial resolutions. Importantly, Core B will be operated by highly experienced biochemists and biophysical chemists to ensure highest quality reagents and services.